J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA.
J Biomed Mater Res A. 2022 Mar;110(3):595-611. doi: 10.1002/jbm.a.37312. Epub 2021 Sep 29.
Damage to the nervous system can result in loss of sensory and motor function, paralysis, or even death. To facilitate neural regeneration and functional recovery, researchers have employed biomaterials strategies to address both peripheral and central nervous system injuries. Injectable hydrogels that recapitulate native nerve extracellular matrix are especially promising for neural tissue engineering because they offer more flexibility for minimally invasive applications and provide a growth-permissive substrate for neural cell types. Here, we explore the development of injectable hydrogels derived from decellularized rat peripheral nerves (referred to as "injectable peripheral nerve [iPN] hydrogels"), which are processed using a newly developed sodium deoxycholate and DNase (SDD) decellularization method. We assess the gelation kinetics, mechanical properties, cell bioactivity, and drug release kinetics of the iPN hydrogels. The iPN hydrogels thermally gel when exposed to 37°C in under 20 min and have mechanical properties similar to neural tissue. The hydrogels demonstrate in vitro biocompatibility through support of Schwann cell viability and metabolic activity. Additionally, iPN hydrogels promote greater astrocyte spreading compared to collagen I hydrogels. Finally, the iPN is a promising delivery vehicle of drug-loaded microparticles for a combinatorial approach to neural injury therapies.
神经系统损伤可导致感觉和运动功能丧失、瘫痪，甚至死亡。为了促进神经再生和功能恢复，研究人员采用生物材料策略来治疗周围和中枢神经系统损伤。可注射水凝胶模拟天然神经细胞外基质，特别适用于神经组织工程，因为它们为微创应用提供了更大的灵活性，并为神经细胞类型提供了一个有利于生长的基质。在这里，我们探索了源自去细胞化大鼠周围神经的可注射水凝胶（称为“可注射周围神经 [iPN] 水凝胶”）的开发，该水凝胶采用新开发的脱氧胆酸钠和 DNA 酶 (SDD) 去细胞化方法进行处理。我们评估了 iPN 水凝胶的胶凝动力学、机械性能、细胞生物活性和药物释放动力学。iPN 水凝胶在 37°C 下不到 20 分钟即可热凝胶化，并且具有类似于神经组织的机械性能。水凝胶通过支持雪旺细胞活力和代谢活性表现出体外生物相容性。此外，iPN 水凝胶比胶原 I 水凝胶更能促进星形胶质细胞的铺展。最后，iPN 是载药微球的有前途的递送载体，可用于联合治疗神经损伤。
